The urinary excretion of orotic acid was investigated in four sheep. Nitrogen and energy intake were varied by infusions of urea and glucose. The effect of arginine infusion was also investigated. Nitrogen intake of 10.4 g/d led to a urinary excretion of orotic acid of 357 +/- 61 micrograms/d. Increasing N intake to 21.4 g/d significantly increased urinary orotic acid excretion to 747 +/- 46 micrograms/d. Glucose infusion (300 g/d) significantly decreased orotic acid excretion when N intake was 10.4 g/d, whereas arginine infusion (2.3 g/d) did not alter the excretion of orotic acid under these conditions. When arginine was infused at higher N intake (21.4 g/d), orotic acid excretion decreased from 822 +/- 74 to 624 +/- 46 micrograms/d. It is concluded that increasing N intake is accompanied by an enhanced urinary excretion of orotic acid. This excretion of orotic acid is significantly modified by glucose or arginine.